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Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L983-L1001. doi: 10.1152/ajplung.00178.2014. Epub 2015 Mar 13.

Utility of large-animal models of BPD: chronically ventilated preterm lambs.

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Department of Pediatrics, University of Utah, School of Medicine, Salt Lake City, Utah; Department of Medicine, University of Utah, School of Medicine, Salt Lake City, Utah; and Department of Neurobiology and Anatomy, University of Utah, School of Medicine, Salt Lake City, Utah


This paper is focused on unique insights provided by the preterm lamb physiological model of bronchopulmonary dysplasia (BPD). Connections are also made to insights provided by the former preterm baboon model of BPD, as well as to rodent models of lung injury to the immature, postnatal lung. The preterm lamb and baboon models recapitulate the clinical setting of preterm birth and respiratory failure that require prolonged ventilation support for days or weeks with oxygen-rich gas. An advantage of the preterm lamb model is the large size of preterm lambs, which facilitates physiological studies for days or weeks during the evolution of neonatal chronic lung disease (CLD). To this advantage is linked an integrated array of morphological, biochemical, and molecular analyses that are identifying the role of individual genes in the pathogenesis of neonatal CLD. Results indicate that the mode of ventilation, invasive mechanical ventilation vs. less invasive high-frequency nasal ventilation, is related to outcomes. Our approach also includes pharmacological interventions that test causality of specific molecular players, such as vitamin A supplementation in the pathogenesis of neonatal CLD. The new insights that are being gained from our preterm lamb model may have important translational implications about the pathogenesis and treatment of BPD in preterm human infants.


airway expiratory resistance; alveolar simplification; alveolarization; endothelial nitric oxide synthase; epigenetics; insulin-like growth factor-1; nasal CPAP; neonatal chronic lung disease; nitric oxide; pulmonary hypertension; vitamin A

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